ANTIARRHYTHMIC DRUGSANTIARRHYTHMIC DRUGS

Every hour

2000 patients around the world die from sudden arrhythmia

attack

CARDIAC ARRHYTHMIAS, LOCAL CAUSESCARDIAC ARRHYTHMIAS, LOCAL CAUSES

CARDIAC CARDIAC ARRHYTHMIASARRHYTHMIAS

SYSTEMIC SYSTEMIC CAUSESCAUSES

Extrasystolia, scintillating arrhythmia, Extrasystolia, scintillating arrhythmia, paroxysmal tachycardia, fibrillationparoxysmal tachycardia, fibrillation

Causes Mechanisms

Surplus of catecholamines (thyreotoxicosis)

Increasing of frequency of spontaneous diastolic depolarization (calcium type) in Р-cells of sinus node

Disturbance of ion balance (hypopotassiumemia, hypomagnesiumemia), ischemia, hypoxia of myocardium, intoxication (cardiac glycosides)

Development of sodium ("fast") type of spontaneous depolarization in elements of conductive system of the heart which don’t have automatism in normal conditions

Insufficient power of potential which exits from sinus node

Manifestation of activity of heterotopous source of impulse development

Disturbance of conductivity Local circulation of impulses(re-entry mechanism)

Scheme of mechanism of repeated entryScheme of mechanism of repeated entry

norm

Nervous impulse

Wall of the ventricles

Impulse goes in reverse direction and enters the starting point (circulation of the impulse),

which leads to out of order and non regular contraction of the heart

12

One-side blockade

Arrhythmia riskier in athletesArrhythmia riskier in athletes

Cardiac problems like Cardiac problems like an abnormal an abnormal heartbeat are heartbeat are exacerbated by exacerbated by rigorous exercise in a rigorous exercise in a way that can be fatal way that can be fatal in athletes, and in athletes, and regular testing for the regular testing for the problem could save problem could save liveslives

Drugs can provoke arrhythmias Drugs can provoke arrhythmias (arrhythmogenic action)(arrhythmogenic action)

All antiarrhythmics All antiarrhythmics except beta-except beta-adrenoblockersadrenoblockers

AntidepressantsAntidepressants

AdrenomimeticsAdrenomimetics

Some antiallergics Some antiallergics (terfenadine=telfast)(terfenadine=telfast)

Supra ventricular tachyarrhythmiasSupra ventricular tachyarrhythmias

VENTRICULAR ARRHYTHMIASVENTRICULAR ARRHYTHMIAS

Classification of antiarrhythmic drugs accordingly Classification of antiarrhythmic drugs accordingly to Williams and Harrison (1970, 1981)to Williams and Harrison (1970, 1981)

Class Mechanism of action Drugs

II Membrane stabilizing, sodium canals blockers

I АI А Slow down Na+ ions entry into cells moderately (0-phase of action potential), considerably prolong (during phase 3) action potential and repolarization duration

Chinidine, novocainamid, disopyramid, aimalin, imipramin, primalin etc.

I BI B Weakly influence on Na+ ions entry, shorten repolarization duration and action potential

Lidocain, trimecain, mexyletin, tokainid, difenin

I СI С Considerably depress Na+ ions entry but almost don’t influence on repolarization period and action potential duration

Flecainid, encainid, ethmosin, ethacisin, alapinin, propaphenon

IIII Beta-adrenergic receptors blockers Anaprilin, nadolol, esmolol, atenolol, methoprolol, bisoprolol

IIIIII Prolong repolarization and action potential (potassium canals blockers)

Amiodaron, brethylium, d-sotalol, nibentan etc.

IVIV Calcium canals blockers Verapamil, galopamil, dilthiazem, bepridil

5th Bradycardiaс agents Alinidin

6th Purinergic receptors stimulants Adenosine, ATP

Indications for using Chinidine sulfateChinidine sulfate (I-А class)

Stabile form of scintillating arrhythmia

Stopping of scintillating arrhythmia

paroxysms

Ventricular extrasystolia and tachycardia (rarely)

Supporting of normal rhythm after cardio version (electro-impulse therapy)

Complications Complications оf chinidine sulfatechinidine sulfate

1. Sinus bradycardia2. Cardiac insufficiency

3. Pirouette tachycardia (“torsade de points” -

polymorphic ventricular tachycardia)4. Thromboembolia

5. Hypotension 6. Nausea, vomiting

7. Ringing in ears, hearing disorders8. Eyesight (vision) disorders

9. Skin rash10. Agranulocytosis (bone marrow suppression)

11. Hepatitis etc.

Indications for administration ofNovocain amidNovocain amid (I-А class)

1. Paroxysms of scintillating arrhythmia (in a case when verapamilum and ATP are ineffective)

2. Fibrillation of atria

3. Prophylaxis and treatment of paroxysmal ventricular tachycardia, extrasystolia

• Allergic reactions (cross-allergic reactions with other Allergic reactions (cross-allergic reactions with other drugs of PABA structure)drugs of PABA structure)

• Nausea, vomitingNausea, vomiting• Insomnia, headache Insomnia, headache

• SeizuresSeizures•Arterial hypotensionArterial hypotension

• Disorders of conductivity and contractility of Disorders of conductivity and contractility of myocardium myocardium

• Arrhythmogenic actionArrhythmogenic action• Leukopenia, agranulocytosisLeukopenia, agranulocytosis• Symptoms of system lupusSymptoms of system lupus

Complications Complications of of novocainamidnovocainamid

Pulsnorma (aimalin)(I-А class)

Indications for administration

Lidocain (I В class)Lidocain (I В class)

It is a drug of choice in case of heavy ventricular

arrhythmias (extrasystolia, paroxysmal tachycardia,

fibrillation) of different origin, including acute

myocardial infarction (0,2 % sol. i. v. very slowly)

Difenin (I В class)Difenin (I В class)

To treat tachyarrhythmias caused by intoxication

with cardiac glycosides

Antiarrhythmic drugs of І С class

ethmosin ethacysin

Atrial and ventricular paroxysmal tachycardia, extrasystolia

Ventriculartachyarrhythmias

Nowadays it is recommended to limit administration of 1 C class drugs using only for the most life threatening

ventricular arrhythmias with considerable clinical symptoms

IIСС classclass

-adrenoblockers (II class)

(anaprilin, atenolol, methoprolol)(anaprilin, atenolol, methoprolol)

Administration: sinus tachycardia (for thyrotoxicosis), supraventricular extrasystolia, paroxysmal tachycardia, including acute myocardial infarction

Contraindications:Contraindications: bronchial asthma, diabetes mellitus, diseases of peripheral vessels, atrioventricular blockade

Anaprilin

Atenolol

Vasocardin (Methoprolol tartrateMethoprolol tartrate)

Potassium canals blockers (III class)Potassium canals blockers (III class)

(amiodaron, brethylium, sotalol)

Usage: atrial and ventricular tachyarrhythmias

AmiodaronAmiodaron drug of choice in case of drug of choice in case of paroxysmal scintillating paroxysmal scintillating

arrhythmia and malignant arrhythmia and malignant ventricular disorders of rhythmventricular disorders of rhythm

Amiodaron

Scheme of amiodaron administration

І - Saturation period (1,5-2 weeks):

200 mg 2-3 times daily

ІІ – Supporting therapy:

200 mg daily 5 days, 2-days brake, after - a certain period of time accordingly to this scheme

Arrhythmil Arrhythmil ((amiodaronamiodaron))

Amiodaron

Amiodaron induced skin Amiodaron induced skin discolorationdiscoloration

Amiodaron induced pulmonary infiltratesAmiodaron induced pulmonary infiltrates

Calcium canals blockers (IV class)Calcium canals blockers (IV class)

(verapamil, dilthiazem)

Administration

supraventricular tachyarrhythmias supraventricular tachyarrhythmias

(paroxysmal tachycardia, extrasystolia, (paroxysmal tachycardia, extrasystolia,

scintillating arrhythmia)scintillating arrhythmia)

Finoptin (verapamil)

VerapamilumVerapamilum

Combination of Combination of verapamilum verapamilum and and digoxinum digoxinum can cause acute digoxine intoxication (they can cause acute digoxine intoxication (they compete for binding with plasma proteins)compete for binding with plasma proteins)

I.v. I.v. verapamileverapamile introduction on the basis of introduction on the basis of ββ-adrenoblockers-adrenoblockers administration can provoke administration can provoke severe bradycardia, severe bradycardia, heart blockade and acute heart blockade and acute hypotensionhypotension

ADENOSINTRIPHOSPHATE (ATP)ADENOSINTRIPHOSPHATE (ATP)

AdministrationAdministration – – supraventricular arrhythmias supraventricular arrhythmias

(i. v. by bolus)(i. v. by bolus)

ComplicationsComplications

ATP introduction after ATP introduction after ββ-adrenoblockers -adrenoblockers can provoke syno-atrial node depression and can provoke syno-atrial node depression and even cardiac arresteven cardiac arrest

When vasospastic type of IHD – ATP When vasospastic type of IHD – ATP introduction can lead to severe angina attackintroduction can lead to severe angina attack

Specific antagonist of ATP - theophyllineSpecific antagonist of ATP - theophylline

Choice of antiarrhythmic agent depending on kind of tachyarrhythmia

• supraventricular tachyarrhythmiassupraventricular tachyarrhythmias – verapamil, beta-adrenoblockers, cardiac glycosides

• ventricular tachyarrhythmiasventricular tachyarrhythmias – lidocain, trimecain, mexyletin, phenitoin (diphenin), ornide, flecainid, rhythmilen

• effective in both caseseffective in both cases - for supraventricular and ventricular tachyarrhythmias – chinidine, novocainamid, ethmosyn, ethacysyn, amiodaron, sothalol, potassium preparates

Administration of antiarrhythmic drugs due to life-threatening

indications

1. frequent and polytopic extrasystoles – manifestations of possible fibrillation

2. constant and paroxysmal ventricular

tachycardia

3. fibrillation of ventricles

4. atrial rhythm disorders, if accompanied by considerable haemodynamic disorders

Administration of antiarrhythmic drugs

Class IType of

arrhythmia

Atrium arrhythmia

Fibrillationof atria

chinidine

amiodaron

anaprilin verapamil digoxin

anticoagulant therapy

The most widely used drug The alternative drug

Class II Class III Class IV others

!This arrhythmia is accompanied by multiple ectopic seats of impulses in atria, which leads to increasing of frequency of ventricular contractions (100-150 beats per minute), which becomes irregular

Antiarrhythmic drugs

Scintillation of atria

Beta-blockers – are the drugs of choicein case of atria fibrillation.

Long lasting administration of anticoagulants in small doses decreases

risk of stroke associated withfibrillation of atria

lidocain

anaprilin

Supraventriculartachycardias

Mechanism ofreentry

Acute supraventricular

tachycardia

anaprilin verapamil digoxin

verapamil adenosine

CONDUCTION OF IMPULSE THROUGH ATRIO-

VENTRICULAR NODE CAN BE SLOWED DOWN BY:

ANAPRILIN, VERAPAMIL,

DIGOXIN

Ventricular tachycardias

Acuteventricular tachycardia

Fibrillation ofventricles

(the previous defibrillation is

not effective)

lidocain

Sotalol,amiodaron

brethylium,amiodaron

adrenalin

This arrhythmia is an often cause of deathof patinets with myocardium infarction.

It can be quickly transformed into fibrillation of ventricles. It needs an immediate treatment.

chinidine

Influence of prolonged administration of antiarrhythmic drugs on mortality

(results of placebo-controlled multicenter randomized trials)

mortality increasingincreasing

mortality decreasingdecreasing

Can possibly decrease mortality (modern data is not convincing)

encainidflecainidmoracisin

beta-adrenoblockers

amiodarondysopyramidmexylethyn

novocainamidpropaphenon

chinidinesotalol

?

MANAGEMENT of ATRIOVENTRICULAR MANAGEMENT of ATRIOVENTRICULAR BLOCKADEBLOCKADE

M-cholinoblockers (atropine)M-cholinoblockers (atropine)

ββ-adrenomimetics -adrenomimetics ((isadrineisadrine))

GlucagonGlucagon

Calcium preparationsCalcium preparations

diphenylhydantoindiphenylhydantoin